Arachidonic acid-induced malondialdehyde formation in rat platelets - Kinetic aspects and inhibition by acetylsalicylic acid and indomethacin

G. de Gaetano, G. Rajtar, M. Livio, J. Merino

Research output: Contribution to journalArticle

Abstract

Malondialdehyde (MDA) is a stable product of arachidonic acid metabolism, catalyzed by the enzyme cyclo-oxygenase. The experimental conditions for measuring the kinetic of MDA formation in rat platelet-rich plasma were defined. In platelets stimulated with arachidonic acid MDA formation was almost linear for a limited period of time (between 0 and 2 min) and was concentration-dependent with saturation kinetics. The hyperbolic curves obtained were recast in a linear plot (according to transformation S/V versus S) and straight lines fitting all experimental points were obtained. The apparent Km value of arachidonic acid was 0.49±0.09 mM and Vmax 1.44±0.06 nmoles MDA/1.4×109 platelets/min. The apparent type of inhibition and the relative potency of acetylsalicylic acid and indomethacin on MDA formation were also investigated. Inhibition by both drugs was concentration-dependent, and was much stronger when either drug was preincubated with platelets for 10 min than for 1 min. Analysis of the data by Dixon plots (1/V versus inhibitor concentrations) revealed an apparently competitive type of inhibition. It is suggested that both acetylsalicylic acid and indomethacin inhibit cyclo-oxygenase in platelet-rich plasma by a similar mechanism, not involving covalent binding of either drug to the enzyme.

Original languageEnglish
Pages (from-to)85-89
Number of pages5
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume312
Issue number1
DOIs
Publication statusPublished - May 1980

Keywords

  • Acetylsalicyclic acid
  • Arachidonic acid metabolism
  • Blood platelets
  • Indomethacin
  • Kinetic analysis
  • Malondialdehyde

ASJC Scopus subject areas

  • Pharmacology

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